Ms T, a 22-year-old, presents to you with her third episode of major depression. Her referring doctor—a very competent family physician—tells you that Ms T "has been tried on everything, and nothing seems to help her." Indeed, the patient has taken 5 different antidepressants in the past 4 years and in each case she "felt like crawling out of her skin." Although the referring physician described the patient as having developed a "tolerance" to various antidepressants, this phenomenon was not ameliorated by increasing the antidepressant dosage, as might be expected with true pharmacological tolerance. Rather, the patient would often feel even worse. The doctor insists that she did a careful evaluation for bipolar disorder and found that "there's no personal or family history of any mania. Ms T just gets depressed."
In your office, the patient appears quite irritable, sometimes answering in a loud voice, "I've been through these questions before! I'm sick of them!" Nevertheless, she is also psychomotorically retarded and shows a long lag phase between question and response. Over the past 3 months, the patient has gained about 16 lb, mainly as a result of "stuffing [herself] with potato chips and chocolate." She sleeps around 12 hours per day but still feels lethargic, "like all the blood has been drained out of me."
Results of physical examination and laboratory testing, including thyroid function, have been within normal limits. Ms T's first major depressive episode occurred at age 16 and presented with similar features, as did her second bout at age 20. During the second episode, the patient developed the idea that "God must think I deserve this," and she could not be dissuaded of this belief by her clergyperson. At that time, she was treated with a low dose of risperidone (Risperdal) and emerged from the depression within a month. Her previous depressive episodes also lasted about a month.
During the present episode, the patient states, "Maybe I'm just a rotten person, so I deserve to rot." The patient denies having any episodes that are consistent with mania, as per the referring physician. There is no clear evidence of frank hypomanic episodes fitting all DSM-IV criteria. The patient's mother, who accompanies her, confirms this. However, the patient adds, "Just before I crashed this time, I was, like, going a mile a minute for a day or two. I cleaned my room all night long and spent half my savings account in one day." The patient's family history is apparently negative for frank bipolar disorder or psychiatric treatment, but her mother and a maternal aunt suffer from "bad mood swings" and heavy alcohol use. Response to trials of fluoxetine (Prozac, Sarafem), sertraline (Zoloft), paroxetine (Paxil), trazodone (Desyrel), and duloxetine (Cymbalta) led to the patient feeling "wired" and "like biting people's heads off"—but not to any frank "switching" into mania or hypomania (using DSM-IV criteria).
As the consulting psychiatrist, what do you recommend to the family physician, the patient, and her mother?
Bipolar boundaries, bipolar depression
As noted many times over the years, the construct of "bipolar spectrum disorder" remains a work in progress.1-4 Few of us doubt it exists—but its precise boundaries are still a matter of considerable debate. Similarly, whereas many of us—this writer included—believe that bipolar disorder is frequently missed, some psychiatrists are convinced that it is widely overdiagnosed. It is possible that—depending on the clinician and the clinical setting—both views are correct. But in my 15-year experience as a psychopharmacology consultant, the outpatients sent to me with so-called treatment-resistant depression almost always wind up with a diagnosis of (missed) bipolar spectrum disorder.
Most of them, like Ms T, have been on numerous antidepressant trials with little or no benefit. Most of them describe their experience with antidepressants in the same dysphoric terms used by Ms T. Most have never had a frank manic episode or even a full-fledged DSM-IV-classified hypomanic episode. Many of them report, like Ms T, periods of unusually elevated mood or energy lasting perhaps a day or two that is sometimes followed swiftly by a depressive "crash." Indeed, with the phenotypic requirement that a hypomanic episode last at least 4 days, DSM-IV criteria may exclude some patients with the genotype for bipolarity. When clinicians look beyond the overly strict DSM-IV criteria for bipolar disorder, we find that as many as 5% to 7% of the general public may have some form of bipolar spectrum disorder.2
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